JP3829305B2 - Melanin production inhibitor - Google Patents

Description

（式中、Ｒは炭素数１０〜２０のアルキル基を示す）で表される化合物を有効成分として含有するメラニン生成抑制剤であって、香粧品などの美白成分として極めて有用である。
【０００９】
【発明の実施の形態】
本発明のメラニン生成抑制剤は、一般式（１）
【００１０】

（式中、Ｒは炭素数１０〜２０のアルキル基を示す）で表される化合物を有効成分として含有するものである。これらのうち、より好ましい化合物は、Ｒが炭素数１０〜１５のアルキル基である化合物、すなわち、３−テトラデセン−４−オリド、３−ペンタデセン−４−オリド、３−ヘキサデセン−４−オリド、３−ヘプタデセン−４−オリド、３−オクタデセン−４−オリド、３−ノナデセン−４−オリドである。
【００１１】
本発明のメラニン生成抑制剤は、例えば、乳液、ローション、クリーム、パウダー、パック剤、皮膚洗浄剤、ペースト剤、ファンデーション、化粧水、ゲル剤、シャンプー、リンス、ボディーソープ、洗顔料等の化粧品や石鹸、その他皮膚外用剤などの香粧品に好適に用いることができる。
【００１２】
本発明のメラニン生成抑制剤の香粧品への配合割合は、任意に設定することができるが、０．００００１〜１０質量％（以下単に「％」で表す）とすることが好ましく、０．０００１〜５％とすることがさらに好ましく、特に好ましくは０．１〜１．０％である。また、本発明のメラニン生成抑制剤は、たとえばアルブチン、コウジ酸、アスコルビン酸など、他のメラニン生成抑制剤と併用することもできる。また、たとえば、ビタミン、抗酸化剤、抗炎症剤、紫外線吸収剤、冷感剤など他の有効成分を配合することもできる。
【００１３】
本発明のメラニン生成抑制剤は、公知の方法に準じて合成することができる。たとえば、Ｔｅｔｒａｈｅｄｒｏｎ Ｌｅｔｔ．（１９８１），２２（５１），５１９１−５［桑島、浦部］に記載されている方法に従い２−トリメチルシリルフランと過酢酸との反応で容易に合成できる。
【００１４】
【実施例】
以下、本発明を実施例により具体的に説明するが、本発明はこれらによって何ら限定されるものではない。
【００１５】
［実施例１] Ｂ１６メラノーマ細胞を用いたメラニン生成抑制試験
（試験方法）
Ｂ１６メラノーマ細胞を播種し、２４時間後サンプルを含有したテオフィリン入り培地に交換し、７２時間後細胞を１０％ＴＣＡ処理した後エタノール：ジエチルエーテル＝１：１で処理し、さらに１０％ＤＭＳＯを含有する１ｍｏｌ／ＬＮａＯＨ液にメラニンを溶解させ、ＯＤ４７５を測定し、メラニン量とした。また、同時に細胞数も求め、細胞当たりのメラニン合成量を算出した。
【００１６】
（計算式）
抑制率（％）＝（Ａ−Ｂ）／Ａ×１００（但し、Ａ：サンプル無添加時の細胞当たりのメラニン合成量、Ｂ：サンプル添加時の細胞当たりのメラニン合成量）
【００１７】
結果を表１に示す。
【００１８】
【表１】
Ｂ１６メラノーマ細胞を用いたメラニン生成抑制試験結果

【００１９】
表２の結果から明らかなように、本発明のメラニン生成抑制剤は、Ｂ１６メラノーマ細胞に対して、優れたメラニン生成抑制効果を示した。また、炭素鎖が長い方が細胞内のメラニン生成を抑制する効果が高いことが確認された。
【００２０】
（香気の評価）本発明のメラニン生成抑制剤について、化合物の香気を評価した。評価方法は、専門パネラー５名による５段階評価にて行った。その結果、３−ヘプテン−４−オリドは、フルーティグリーン、バルサミック、スパイシーな好ましい香気で、香気強度評価の平均点は４点とかなり強い香気を有すると評価されたのに対し、３−テトラデセン−４−オリドは、フルーティグリーン、バルサミック、スパイシーな好ましい香気であるが、香気強度評価の平均点は１．８点で、香気を有するものの非常に弱いとの評価であった。このことから、本発明の化合物群は、全体に好ましい香気を有し、側鎖部分の炭素数を延長することにより、さらに香気を押さえることが可能であることを確認した。
【００２１】
【発明の効果】
本発明の一般式（１）で表される化合物は、高いメラニン生成抑制効果を有し、それ自身の香気強度が低いため、香粧品の品質を損なったり、香粧品の香りのバリエーションを限定することがなく、任意の量を配合することが可能であり、香粧品中に安全に用いることができる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to melanin production inhibitors and cosmetics containing them.
[0002]
[Prior art]
Conventionally, the suppression of melanin production is due to cytotoxicity to melanocytes, the suppression of tyrosinase activity in melanocytes, the suppression of tyrosinase expression, the autooxidation from dopaquinone generated by tyrosinase activity There is known a method for preventing oxidation through a route leading to melanin. And hydroquinone etc. are known as what shows the melanin production suppression effect by cytotoxicity. They have been used to treat pigmentation for the purpose of reducing skin pigmentation, but have safety issues. Arbutin, which is generally known as a derivative thereof, is generally used in cosmetics and the like as a substance that reversibly suppresses the production of melanin.
[0003]
Other melanin production inhibitors include, for example, cysteine, glutathione, vitamin C (Non-patent document 1), kojic acid (Non-patent document 2), products of microorganisms belonging to the genus Trichoderma (patent document 1), and alkalis of milk proteins. Decomposed product (Patent Document 2), hydrolyzate of milk protein (Patent Document 3), amino acid derivative and peptide derivative of kojic acid (Patent Document 4), fragrance compound group having melanin production inhibitory function (Patent Document 5), tyrosinase A group of perfume compounds having an activity-inhibiting function (Patent Documents 6 and 7), various plant extracts, and the like are known.
[0004]
However, these conventional melanin production inhibitors are problematic in terms of safety like hydroquinone, the effects are not satisfactory in practice, or the odor of the melanin production inhibitor is a problem. . In addition, the fragrance compound group having a melanin production inhibitory function also has a preferable fragrance itself, but when adding a desired fragrance to the product from the fragrance balance of the product, the blending amount of the melanin production inhibitor is free. It could not be said that it was really satisfying because it was difficult to set to.
[0005]
[Patent Document 1]
Japanese Patent Laid-Open No. 2-145189 [Patent Document 2]
Japanese Patent Publication No.58-17773 [Patent Document 3]
JP-A-5-320068 [Patent Document 4]
JP-A-4-187618 [Patent Document 5]
JP 2000-302642 A [Patent Document 6]
JP 2001-163719 A [Patent Document 7]
JP 2001-240528 A [Non-Patent Document 1]
Mishima Yutaka et al., Basic Dermatology, page 258, Asakura Shoten, 1973 [Non-patent Document 2]
Nikkei Business Daily, May 24, 1988 [0006]
[Problems to be solved by the invention]
An object of the present invention is to provide a melanin production inhibitor that is safe and can be incorporated in an arbitrary amount in a cosmetic product without impairing the quality of the cosmetic product.
[0007]
[Means for Solving the Problems]
The melanin production inhibitor of the present invention has the following general formula (1):
[0008]

(In the formula, R represents an alkyl group having 10 to 20 carbon atoms) A melanin production inhibitor containing a compound represented by an active ingredient, and is extremely useful as a whitening ingredient for cosmetics and the like.
[0009]
DETAILED DESCRIPTION OF THE INVENTION
The melanin production inhibitor of the present invention has the general formula (1)
[0010]

(In the formula, R represents an alkyl group having 10 to 20 carbon atoms) and contains as an active ingredient. Among these, more preferable compounds are compounds in which R is an alkyl group having 10 to 15 carbon atoms, that is, 3-tetradecene-4-olide, 3-pentadecene-4-olide, 3-hexadecene-4-olide, 3 -Heptadecene-4-olide, 3-octadecene-4-olide, 3-nonadecene-4-olide.
[0011]
The melanin production inhibitor of the present invention includes, for example, cosmetics such as emulsions, lotions, creams, powders, packs, skin cleansers, pastes, foundations, lotions, gels, shampoos, rinses, body soaps, facial cleansers, etc. It can be suitably used for cosmetics such as soap and other skin external preparations.
[0012]
The blending ratio of the melanin production inhibitor of the present invention into the cosmetic can be arbitrarily set, but is preferably 0.00001 to 10% by mass (hereinafter simply referred to as “%”), 0.0001 It is more preferable to set it to -5%, Especially preferably, it is 0.1-1.0%. Moreover, the melanin production inhibitor of this invention can also be used together with other melanin production inhibitors, such as arbutin, kojic acid, ascorbic acid, for example. In addition, for example, other active ingredients such as vitamins, antioxidants, anti-inflammatory agents, ultraviolet absorbers, and cooling agents can be blended.
[0013]
The melanin production inhibitor of the present invention can be synthesized according to a known method. For example, Tetrahedron Lett. (1981), 22 (51), 5191-5 [Kuwashima, Urabe], and can be easily synthesized by the reaction of 2-trimethylsilylfuran and peracetic acid.
[0014]
【Example】
EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited to these examples.
[0015]
[Example 1] Inhibition test of melanin production using B16 melanoma cells (test method)
B16 melanoma cells were seeded and replaced with theophylline-containing medium containing the sample after 24 hours. After 72 hours, the cells were treated with 10% TCA, treated with ethanol: diethyl ether = 1: 1, and further containing 10% DMSO. Melanin was dissolved in 1 mol / L NaOH solution, and OD475 was measured to obtain the amount of melanin. At the same time, the number of cells was determined, and the amount of melanin synthesis per cell was calculated.
[0016]
(a formula)
Inhibition rate (%) = (A−B) / A × 100 (where A: amount of melanin synthesis per cell when no sample is added, B: amount of melanin synthesis per cell when sample is added)
[0017]
The results are shown in Table 1.
[0018]
[Table 1]
Results of melanin production inhibition test using B16 melanoma cells

[0019]
As is clear from the results in Table 2, the melanin production inhibitor of the present invention showed an excellent melanin production inhibitory effect on B16 melanoma cells. In addition, it was confirmed that the longer the carbon chain, the higher the effect of suppressing intracellular melanin production.
[0020]
(Evaluation of fragrance) The odor of the compound was evaluated for the melanin production inhibitor of the present invention. The evaluation method was a five-step evaluation by five specialized panelists. As a result, 3-heptene-4-olide is a fruity green, balsamic, and spicy preferred fragrance, and the average score of fragrance intensity evaluation was evaluated as 4 points, while it was evaluated to have a fairly strong fragrance. -4-Olide is a fruity green, balsamic, and spicy preferred fragrance, but the average score of the fragrance strength evaluation was 1.8 points, and it was evaluated that it had a fragrance but was very weak. From this, it was confirmed that the compound group of the present invention has a preferable fragrance as a whole and can further suppress the fragrance by extending the carbon number of the side chain portion.
[0021]
【The invention's effect】
The compound represented by the general formula (1) of the present invention has a high melanin production-inhibiting effect and its own fragrance strength is low, so that the quality of the cosmetic product is impaired or the variation of the fragrance of the cosmetic product is limited. It is possible to mix | blend arbitrary quantity, and can use it safely in cosmetics.

Claims (3)

General formula (1)

A melanin production inhibitor containing a compound represented by the formula (wherein R represents an alkyl group having 10 to 20 carbon atoms) as an active ingredient. The compound represented by General formula (1) is 3-tetradecene-4-olide, The melanin production inhibitor characterized by the above-mentioned. Cosmetics containing the melanin production inhibitor according to claim 1 or 2.